Age-related hip fractures are an escalating public health problem, with over 280,000 hip fractures occurring each year in the US and costs in excess of $10 billion. The long-term objectives of this application are to understand the biomechanical factors that influence hip fracture risk, and to develop non-invasive densitometric measures that can be used clinically for fracture risk prediction. During the previous funding period, the applicant demonstrated that strong associations between bone mineral density (BMD) and fracture load hold over a wide range of age and loading rates. He has also shown that factors related to fall severity (fall direction, impact site, and potential energy) exert a strong and potentially dominant influence on fracture risk and touch on a domain of risk independent of bone density. To address the confounding influences of body habitus and fall severity, a composite index has been proposed that the applicant calls the factor of risk. The applicant has shown, in a limited, retrospective, case-control study, not only a strong association between the factor of risk and hip fracture, but a stronger association with hip fracture than femoral BMD alone. The applicant now proposes to extend these studies in several important ways. Aim 1 will examine the role of muscle forces, both from fall- related impact and during several common activities of daily living, thereby estimating the factor of risk for loads that could cause spontaneous fractures. Aim 2 will develop methods for predicting failure of the proximal femur using finite element models. These methods wull be used to examine the effect of loading conditions and age- related density changes on fracture risk. These models will also be used to examine potential reductions in fracture risk induced by bisphosphonate therapy. In Aim 3, the confounding influence of body habitus on hip fracture risk will be characterized by conducting a series of ex vivo experiments using soft tissues and matching femurs from donors of known height and weight. The findings will help refine their estimates of the factor of risk for a given body habitus, gender and fall direction. Finally, in Aim 4, the factor of risk will be tested by conducting a prospective study of elderly nursing home subjects. At baseline, subject height, weight, body mass index and trochanteric soft tissue thickness will be assessed to estimate the hip impact forces from a fall (numerator of factor of risk) and hip bone mineral density to estimate femoral strength (the denominator of factor of risk). The applicant hypothesizes that the factor of risk will not only associate strongly with hip fracture incidence, but will be a better predictor of hip fracture risk than BMD alone. With intervention strategies based on an improved understanding of the complex interplay between fall biomechanics and bone fragility, the applicant believes there is hope that the growing epidemic of hip fractures among the elderly can be substantially abated.